Efficacy and safety of albendazole in hookworm-infected preschool-aged children, school-aged children and adults in Côte d'Ivoire: a phase II randomized controlled dose-finding trial

BACKGROUND: Infections with hookworms affect about half a billion people worldwide. Recommended therapy includes 400 mg of albendazole, which is moderately efficacious. Higher doses have been rarely assessed. METHODS: A randomized controlled dose-finding trial was conducted in a low transmission setting in Cote d'Ivoire aiming to recruit 120 preschool-aged children (PSAC), 200 school-aged children (SAC) and 200 adults. Eligible PSAC were randomized 1:1:1 to 200 mg, 400 mg, or 600 mg of albendazole, the other age groups 1:1:1:1:1 to placebo or 200 mg, 400 mg, 600 mg, or 800 mg. The primary outcome was cure rates (CRs) assessed 14-21 days post-treatment by quadruplicate Kato-Katz thick smears. Hyperbolic Emax models were used to determine dose-response. RESULTS: 38 PSAC, 133 SAC, and 196 adults were enrolled. In adults, predicted CRs increased with ascending doses of albendazole with a CR of 74.9% (95% Confidence Interval: 55.6%-87.7%) in the 800 mg arm. Observed CRs increased with ascending doses of albendazole and reached a maximum of 94.1% (95% CI: 80.3%-99.3%). In SAC, the predicted dose-response curve increased marginally with CRs ranging from 64.0% in the 200 mg to 76.0% in the 800 mg arm. Sample size in PSAC was considered too small to derive meaningful conclusions. Only 10.7% and 5.1% of participants reported any adverse event at 3 hours and 24 hours post-treatment, respectively. CONCLUSIONS: A single 800 mg albendazole dose provides higher efficacy against hookworm and is well tolerated in adults and should be considered for community-based strategies targeting adults. For PSAC/SAC, current recommendations suffice.